Polycythemia vera is a rare, chronic condition affecting the blood, characterized by the bone marrow producing an excessive number of red blood cells. This overproduction can lead to the blood becoming thicker, increasing the risk of various complications. Diagnosing this condition involves a thorough, multi-step investigative process, guided by an internationally recognized framework to ensure accuracy and distinguish it from other disorders.
Initial Blood Test Findings
The first indication of polycythemia vera often emerges from a routine Complete Blood Count (CBC). This initial screening can reveal an abnormally high concentration of red blood cells, which prompts further investigation. Hemoglobin, the protein in red blood cells that carries oxygen, and hematocrit, the percentage of blood volume occupied by red blood cells, are two primary measurements observed.
Elevated levels of hemoglobin (greater than 16.5 grams per deciliter (g/dL) in men or 16 g/dL in women) or hematocrit (exceeding 49% in men or 48% in women) are significant indicators. While these thresholds serve as important guidelines, they are not definitive on their own but signal a need for more specialized testing. The CBC might also show an increase in white blood cells and platelets, suggesting a broader issue with blood cell production.
Genetic and Hormone Level Analysis
Following initial abnormal blood counts, specific follow-up blood tests are performed to look for distinct biological markers. The presence of a mutation in the JAK2 gene is a key piece of evidence pointing towards polycythemia vera. The JAK2 V617F mutation is found in approximately 95% of individuals with polycythemia vera, making it a highly indicative marker. This genetic change affects a protein that signals blood cells to grow and divide, leading to uncontrolled production.
In a small percentage of cases (2-3%) where the JAK2 V617F mutation is absent, other mutations in the JAK2 gene, such as those in exon 12, can also be present and confirm the diagnosis. Analyzing the level of erythropoietin (EPO) in the blood provides another important clue. EPO is a hormone produced primarily by the kidneys that stimulates the bone marrow to produce red blood cells. In polycythemia vera, the bone marrow produces red blood cells independently, even when EPO levels are abnormally low. This contrasts with other forms of elevated red blood cell counts, where high EPO levels might be observed as the body tries to compensate for low oxygen.
Bone Marrow Examination
A bone marrow examination, which includes both an aspiration and a biopsy, provides direct insight into the blood-forming tissue. This procedure is performed to confirm the diagnosis and assess the state of the bone marrow. During an aspiration, a small sample of liquid bone marrow is removed using a needle. A biopsy involves taking a small piece of the spongy bone tissue itself. These samples are then examined by a pathologist under a microscope.
The pathologist looks for hypercellularity, meaning the bone marrow is overly crowded with blood-forming cells. There is an increase in the precursors for red blood cells, white blood cells, and platelets, known as trilineage growth. Megakaryocytes, the cells that produce platelets, may also appear altered, appearing pleomorphic or varied in size. While this examination provides direct physical evidence, it may not always be strictly necessary if other diagnostic criteria are definitively met.
Applying the World Health Organization Criteria
The World Health Organization (WHO) provides the globally recognized framework for diagnosing blood disorders, including polycythemia vera. This framework integrates the findings from various tests into a cohesive set of criteria. Adhering to these standards ensures a consistent and accurate diagnosis.
The WHO criteria for polycythemia vera include three major criteria and one minor criterion. The first major criterion involves elevated hemoglobin or hematocrit levels, as detailed in the “Initial Blood Test Findings” section. The second major criterion is the presence of hypercellularity in the bone marrow biopsy, showing increased trilineage growth and characteristic megakaryocyte changes, as described in the “Bone Marrow Examination” section. The third major criterion is the detection of the JAK2 V617F mutation or a JAK2 exon 12 mutation, as discussed under “Genetic and Hormone Level Analysis.”
The single minor criterion is an abnormally low serum erythropoietin level, also mentioned in “Genetic and Hormone Level Analysis.” To establish a formal diagnosis of polycythemia vera, an individual must meet either all three major criteria or the first two major criteria combined with the minor criterion. This comprehensive approach ensures a precise diagnosis.